Chapter 24. Pityriasis Rubra Pilaris

Pityriasis rubra pilaris is a rare, chronic disorder with an estimated incidence ranging from 1 in 5,000 to 1 in 50,000 dermatology patients. The age distribution is bimodal with peak incidences in the first and fifth decades of life. The disease occurs in all races and affects the sexes equally.1

Although an underlying dysfunction in vitamin A metabolism has been suggested, the etiology and pathogenesis of pityriasis rubra pilaris are still poorly understood. Thus, the role of vitamin A deficiency remains uncertain as attempts to produce keratotic lesions by vitamin A deprivation have been unsuccessful. Moreover, the deficiency of retinol-binding protein as an underlying pathogenic mechanism resulting in inadequate transport of vitamin A to the skin has yet to be ascertained. There are some cases in which pityriasis rubra pilaris may result from immune system dysregulation and abnormal response to various antigenic triggers.2 A report of an exanthematous form of juvenile pityriasis rubra pilaris that followed an upper respiratory infection and initially resembled Kawasaki disease supports the hypothesis of a superantigen-mediated process. Finally, genetic factors with an autosomal dominant pattern of inheritance have been supposed to play a critical role for the induction of pityriasis rubra pilaris. Nevertheless, affected relatives are not observed in the classical acute-onset disease and are infrequent in other variants.

Cutaneous Lesions

Pityriasis rubra pilaris is generally believed to comprise more than a single entity and a classification scheme based on clinical characteristics and course has been proposed by Griffiths1 (Table 24-1).

Type I (classic adult) is the most common subtype with over 50% of all cases. Characteristically, patients present with an eruption of follicular hyperkeratotic papules that spread in cephalocaudal direction (Fig. 24-1). As the disease further evolves, a reddish orange, scaling dermatitis appears that often progresses to a generalized erythroderma over a period of 2–3 months (Fig. 24-2). A diagnostic hallmark of pityriasis rubra pilaris are sharply demarcated islands of unaffected skin (“nappes claires”) in a random distribution (Fig. 24-2B). Many patients develop a waxy, diffuse, yellowish keratoderma of the palms and soles (Fig. 24-3).3 Nail changes are not uncommon and include distal yellow–brown discoloration, nail plate thickening, splinter hemorrhages, and subungual hyperkeratosis. Eventually, the mucous membranes may be affected with a diffuse whitish appearance of the buccal mucosa as well as lacy white plaques and erosions. Hair and teeth are normal.

Type II is an atypical variant with onset in adult age. Areas of follicular hyperkeratosis as well as ichthyosiform scaling, especially on the legs, dominate the clinical picture. This variant lacks the typical cephalocaudal progression observed in type I, and there is less tendency for the patients to become erythrodermic. Sparseness of the scalp hair is occasionally seen.

Type III (classic juvenile) typically begins in years 1 or 2 of life and shows all the morphological features of type I (Fig. 24-4).

Type IV (circumscribed juvenile) affects approximately 25% of the patients. This type usually presents several years after birth and is characterized by well-demarcated hyperkeratotic erythematous plaques on the elbows and knees, resembling localized psoriasis. According to Griffith,1 these lesions do not progress to the widespread types I and III. Yet, some cases show marked palmoplantar keratoderma.

Type V is an atypical variant of juvenile pityriasis rubra pilaris that usually presents in the first few years of life and has a more chronic course. This type is distinguished by follicular hyperkeratosis with only minimal erythema and a scleroderma-like appearance of the hands and feet. Most cases of familial pityriasis rubra pilaris belong to this type, which may even represent a different clinical entity sharing features with several poorly defined ichthyotic disorders such as follicular ichthyosis and the erythrokeratodermas.

Other reports have described a type VI variant associated with HIV infection. The clinical features of this variant are similar to type I but with increased severity and additional manifestations of acne conglobata, hidradenitis suppurativa, and lichen spinulosus.

Related Findings

There have been rare cases of a pityriasis rubra pilaris-like eruption, clinically and histologically, in patients with dermatomyositis, often associated with internal neoplasia. Concomitant rheumatologic disorders, mainly inflammatory polyarthritis, have also been reported. In addition, numerous other noncutaneous diseases were considered to be related to pityriasis rubra pilaris, which are probably all fortuitous.

Pathology

Pathological findings in pityriasis rubra pilaris vary according to the duration of the disease. The findings are most likely to be diagnostic in the acute phase, when hyperkeratosis, acanthosis with broad short rete ridges and alternating orthokeratosis and parakeratosis oriented in both horizontal and vertical directions can be observed. Usually, there is a sparse superficial, perivascular lymphocytic infiltrate in the underlying dermis. Keratinous plugs of the follicular infundibula as well as perifollicular areas of parakeratosis may also be present. A prominent granular layer and dilated, but not tortuous capillaries are features that help to distinguish pityriasis rubra pilaris from psoriasis, its most important differential diagnosis.

See Box 24-1.

Systemic symptoms are uncommon except when generalized erythroderma occurs, and then they are comparable to those seen in exfoliative dermatitis (see Chapter 23). Occasionally, a mild ectropion may develop when the face becomes uniformly erythematous. Even though rare, moderate to severe pruritus or burning sensations may occur.

The classic adult disease (type I) usually remits completely within an average of 3 years. However, recurrences are recognized in up to 20% of patients, sometimes after long periods of subclinical disease. In the classic juvenile variant (type III) spontaneous clearing is commonly observed in 1 to 2 years. However, the atypical variants (type II and IV) have a less favorable prognosis for remission, some cases of type IV improve in late teens. Moreover, there is little or no tendency of type V to resolve spontaneously, improvements with retinoids have been described but relapses occurred when treatment was withdrawn. Clinical manifestations in the HIV-associated type VI are severe and occasionally fatal, with death occurring due to complications of cutaneous sepsis.

(Box 24-2)

Patients with pityriasis rubra pilaris are often irresponsive to multiple therapies, both topical and systemic.3 Because of the relative rarity of the disease and its variable course, the chances for clinical trials assessing treatment options have been limited. Previous treatment strategies, which relied on megadoses of oral vitamin A or the anabolic steroid stanazol, proved to be largely ineffective.

Currently, oral retinoids are the first line of therapy in patients with pityriasis rubra pilaris. Isotretinoin has been reported to be of some value, although a comprehensive review suggests that acitretin may be more effective in clearing patients. Accordingly, most patients are treated first with acitretin. Alitretinoin, a novel panagonist retinoid (see Chapter 228), might be an alternative option for systemic treatment in patients refractory to conventional therapy. Treatment with methotrexate, using the guidelines established for psoriasis, has shown variable rates of success. Some cases respond well to photochemotherapy (PUVA), some may flare, and others require combination treatment with retinoids or methotrexate. In patients with severe symptoms, effective amelioration of the disease may require extracorporeal photopheresis but there are no evidence-based data. Immunosuppressive agents are of inconsistent benefit. Thus, controversy persists about the role of cyclosporine in the treatment of pityriasis rubra pilaris. While most studies show lack of efficacy, several cases of adult-type pityriasis rubra pilaris showed significant clearance in 2–4 weeks. Some patients are helped by azathioprine, but this effect is also inconsistent. The use of glucocorticosteroids in the management of pityriasis rubra pilaris has been studied, but there is no evidence to suggest a beneficial effect. Whether phototherapy can be effective is controversial. Ultraviolet B (UVB) irradiation, which is efficiently used for psoriasis, has not been helpful or even worsened pityriasis rubra pilaris. UVA1 phototherapy may be a satisfactory alternative.

When conventional treatment strategies fail, new therapeutic approaches may include the use of immunomodulatory drugs. Fumaric acid esters were reported as successful in inducing remission in a patient with juvenile pityriasis rubra pilaris unresponsive to the usual treatment options.4 Kerr and Ferguson reported a patient with type II adult-onset pityriasis rubra pilaris resistant to multiple therapies whose condition improved markedly with high-dose human intravenous immunoglobulin (IVIg) infusions.5 Moreover, there is accumulating evidence indicating that blockade of tumor necrosis factor (TNF-α), which is beneficial in psoriasis and psoriasis–arthritis, is effective in the adult- and juvenile-onset types of pityriasis rubra pilaris as well.6

Topical treatment with keratolytics (where possible under an occlusive plastic dressing) has proved a valuable mode of adjuvant therapy in pityriasis rubra pilaris. For symptomatic relief, emollients and antihistamines provide significant benefit. Topical therapy with calcipotriol showed encouraging results. Its disadvantage is that total body treatment for the erythrodermic patient could be toxic. Success has been reported with topical aminonicotinamide 1%, although it is not commonly used.3

Pityriasis rubra pilaris associated with HIV infection has responded to triple antiretroviral therapy.7

Present therapeutic options (including drug doses) for pityriasis rubra pilaris used in adults and children are listed in Box 24-2.

Pityriasis rubra pilaris is a rare, but socially and psychologically disabling condition, occurring in children and adults of both sexes. Suicide remains a risk in patients with generalized disease. Therefore, knowledge of the clinical pattern and cutaneous findings is crucial for an early therapeutic intervention, and may prevent protracted illness and serious complications in this clinically challenging condition.